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In mice and men, cells age the same

By amy adams

Stuart Kim

We can dye gray hair, lift sagging skin or boost lost hearing, but no visit to the day spa would be able to hide a newly discovered genetic marker for the toll that time takes on our cells. "We've found something that is at the core of aging," said Stuart Kim, PhD, professor of developmental biology and of genetics at the School of Medicine.

In a study published in the July 21 issue of Public Library of Science-Genetics, Kim and colleagues report finding a group of genes that are consistently less active in older animals across a variety of species. The activity of these genes proved to be a consistent indicator of how far a cell had progressed toward its eventual demise.

Until now, researchers have studied genes that underlie aging in a single animal, such as flies or mice, or in different human tissues. However, a protein associated with aging in one species may not be relevant to the aging function in a different animal. This limitation had made it difficult to study the universal processes involved in aging.

Kim's work overturns a commonly held view that all animals, including humans, age like an abandoned home. Slowly but surely the windows break, the shingles fall off and floorboards rot, but there's no master plan for the decay.

That theory has left open questions about why tortoises and rockfish are still partying like 20-somethings at an age when humans are considered relics. At the other end of the spectrum, flies die off before young humans can even focus their eyes. Clearly, not all cells fall apart at the same rate.

"Aging isn't like the speed of light; it's not a constant," said Kim. Why animals and even people age at different rates prompted Kim to look deeper into the processes that control aging.

His new study suggests that the cell has a molecular homeowner that keeps up repairs until a predetermined time, when the owner picks up the welcome mat and moves out. Once that process kicks off, the decay happens as a matter of course. The homeowners in tortoise cells stick around for hundreds of years delaying the decay, while those in fly cells move out within weeks.

Although Kim's work doesn't identify what triggers that process, it does provide a way of detecting the point a cell has reached in its life span.

In the study, Kim and his colleagues looked at which genes were actively producing protein and at what level in flies and mice and in tissue taken from the muscle, brain and kidney of 81 people ranging in age from 20 to 80. The group used a microarray, which can detect the activity level of all genes in a cell or tissue. Genes that are more active are thought to be making more proteins.

One group of genes consistently made less protein as cells aged in all of the animals and tissues the group examined. These genes make up the cellular machinery called the electron transport chain, which generates energy in the cell's mitochondria.

Kim said the gene activity is a better indicator of a cell's relative maturity than a person's birthday. One 41-year-old participant had gene activity similar to that of people 10 to 20 years older; muscle tissue from the participant also appeared similar to that of older people. Likewise, the sample from a 64-year-old participant, whose muscles looked like those of a person 30 years younger, also showed gene activity patterns similar to a younger person.

The results confirm Kim's assumption that the rate of aging is at least in part genetically determined. Study participants whose tissues appeared younger than their true age had something—something dearly sought by aging researchers—that made their cells keep activating genes in a more youthful pattern.

The question is: What causes the electron transport chain genes to slow their protein production and why? And why, if tortoises can live hundreds of years, do flies self-destruct in a matter of weeks?

Kim suggests that aging wouldn't have to happen if cells weren't programmed to fail. With a marker for aging, he thinks future research will reveal what drives the process. "People think of aging and taxes as unavoidable," Kim said, "but in the case of aging, that's not true."